During the past two decades a significant body of evidence has accumulated showing that metabolic oxidation/reduction reactions represent a significant underlying mechanism contributing to promotion and progression of malignancy, as well as a therapeutic target for selectively sensitizing cancer cells to therapeutic interventions. Evolving in parallel has been the recognition that advanced medical imaging techniques, measuring metabolic changes in cancer versus normal tissues before and during therapy show great promise in allowing non-invasive quantitation and monitoring of fundamental differences in cancer cell metabolism to improve cancer therapy. The Free Radical Metabolism and Imaging (FRMI) Program (32 full members and 9 associate members) representing 3 colleges and 10 departments was formed by a merger in 2014 of former programs in Free Radical Cancer Biology and Tumor Imaging to take full advantage of the convergence of the science in these two disciplines. The FRMI program has four research themes: 1) Free Radical Cancer Biology, the study of fundamental differences in redox biochemistry and its impact on cell signaling, genetics and epigenetics in cancer biology and therapy; 2) Redox-Based Therapeutics, the development and testing of novel cancer therapeutics based on exploiting fundamental differences in free radical metabolism to selectively eradicate cancer cells while protecting normal tissues; 3) Patient Outcomes and Molecular Imaging, the development of novel image- guided therapy approaches for enhancing and predicting patient outcomes in cancer therapy using molecular and metabolic imaging techniques; and 4) Novel Approaches to Diagnostic Imaging, the development of novel approaches that integrate state-of-the-art functional and anatomic imaging techniques into cancer biology and therapy. FRMI members were highly collaborative during the last period of support with a total of 250 cancer relevant publications (2011-2015) including 53% (n=133) involving collaborations between 2 or more members of the HCCC. Of the collaborative publications, 66% (n=88) were intra-programmatic and 60% (n=81) were inter- programmatic. In addition, 30% (n=76) were interinstitutional with members of the program co-authoring 45 publications with faculty members at other cancer centers in the United States. Ten manuscripts were published in high impact journals (impact factor ?10). The program members were supported by $5,857,820 of total peer-reviewed funding and $2,699,266 of NCI funding in the last year of CCSG support. The successful completion of the research initiatives pursued by FRMI would involve preclinical and clinical verification of a paradigm shifting approach for targeting oxidative metabolic processes in cancer cells as indicated by selective enhancement of therapeutic outcomes, and implementation of new image-based approaches to predicting clinical outcomes, monitoring response and guiding decision-making.